VIP: A Comparison of Linear and Cyclic Peptoid Oligomers as Potent Antimicrobial Agents

The emergence of highly pathogenic multidrug-resistant bacteria has spurred an urgent quest for new antibiotic agents. Scientists at New York University (USA) designed a family of molecules that mimic the structures and activities of natural antimicrobial peptides. PhD student Mia Huang, working in the laboratories of bioorganic chemist Prof. Kent Kirshenbaum and microbiologist Prof. Victor Torres, synthesized libraries of linear and cyclic peptidomimetic oligomers known as peptoids. The research explored the relationship between the structures of the peptoid oligomers and their antimicrobial activities against pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Biological assays identified several peptoids that possess selective bactericidal activities without significantly harming human red blood cells. Conformationally constrained cyclic peptoids were generally more potent than their linear counterparts. The in vitro studies indicated that peptoids may be a source of promising lead compounds for drug discovery, as the peptoids exhibit potent antimicrobial activities while deterring the development of antibiotic resistance in MRSA.